Apixaban Orally Disintegrating Tablets for Consistent Dissolution
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Solution Overview
Problem
Existing apixaban formulations face challenges with inconsistent dissolution and absorption due to particle size and manufacturing process, particularly for patients with dysphagia, leading to reduced patient compliance and suboptimal exposure.
Innovation Solution
Development of an orally disintegrating tablet formulation with a specific ratio of apixaban to disintegrating excipients, ensuring consistent dissolution and absorption, with a hardness of 10N to 200N and disintegration time of less than 3 minutes, using direct compression, wet granulation, or dry granulation methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If apixaban is formulated as an immediate release tablet for patients with dysphagia, then the drug can be administered to patients who have difficulty swallowing, but the dissolution and absorption become inconsistent due to particle size and manufacturing process variations
Solution Approach 1:
The patent transforms the immediate release tablet into an orally disintegrating tablet (ODT) with specific physical parameters: hardness of 10N to 200N and disintegration time of less than 3 minutes. This parameter change allows the tablet to disintegrate rapidly in the oral cavity without requiring swallowing, thereby maintaining ease of administration for dysphagic patients while ensuring consistent drug release and absorption through controlled disintegration characteristics.
Solution Approach 2:
The patent employs composite material formulation by combining apixaban with specific excipients including disintegrating excipients (at least 5% w/w), binders, and fillers in optimized ratios. This composite structure creates an orally disintegrating tablet that maintains structural integrity during handling (hardness 10N-200N) while ensuring rapid disintegration (<3 minutes) in the oral cavity, thereby resolving the contradiction between ease of administration and dissolution consistency.
2Strength
If the tablet hardness is increased to improve mechanical strength and handling, then the tablet becomes more robust during manufacturing and distribution, but the disintegration time increases and may exceed 3 minutes
Solution Approach 1:
The patent establishes an optimized parameter range for tablet hardness (10N to 200N) that balances mechanical strength with disintegration performance. Within this range, the tablet maintains sufficient robustness for manufacturing and distribution while ensuring disintegration occurs within less than 3 minutes in the oral cavity, thereby resolving the trade-off between strength and disintegration speed.
Solution Approach 2:
The patent uses composite material composition with specific ratios of binders (5% to 50% w/w) and disintegrating excipients (at least 5% w/w) to achieve the desired balance. The binder provides structural integrity for mechanical strength, while the disintegrating excipient ensures rapid breakdown upon contact with oral fluids, maintaining both hardness requirements and disintegration time specifications simultaneously.
3Ease of manufacture
If apixaban particles with larger size are used to simplify manufacturing, then the manufacturing process becomes less complex, but the dissolution rate decreases and exposure after oral administration becomes suboptimal
Solution Approach 1:
The patent extracts the dissolution limitation by transitioning from an immediate release matrix to an orally disintegrating matrix. This extraction allows the use of coarser apixaban particles (D90 up to 450 μm) that would normally result in suboptimal dissolution, because the rapid disintegration of the ODT formulation in the oral cavity precedes and enhances the dissolution process, thereby maintaining manufacturing simplicity while achieving optimal exposure.
Solution Approach 2:
The patent employs composite material formulation where disintegrating excipients (at least 5% w/w) and binders work synergistically to create a matrix that rapidly disintegrates in the oral cavity. This composite structure enables the use of coarser apixaban particles with consistent dissolution and optimal exposure by ensuring the drug is released quickly upon disintegration, without requiring complex manufacturing processes for particle size reduction.
Data Source
AI summary
The present invention relates to an orally disintegrating pharmaceutical dosage forms of apixaban or a pharmaceutically acceptable salt or prodrug thereof. The present invention specifically relates to a stable orally disintegrating pharmaceutical composition comprising apixaban and one or more pharmaceutically acceptable excipients. Further, the present invention relates to an orally disintegrating dosage form comprising apixaban, at least one disintegrating excipient and optionally one or more pharmaceutically acceptable excipients for treatment of disorders associated with Factor Xa.